11-5778434-C-T

Position:

chr11-5778434-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001385662.1(OR52N5):c.201G>A(p.Met67Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000099 in 1,514,674 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000029 ( 1 hom., cov: 25)

Exomes 𝑓: 0.0000080 ( 0 hom. )

Consequence

OR52N5
NM_001385662.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.59

Variant links:

Genes affected

OR52N5 (HGNC:15231): (olfactory receptor family 52 subfamily N member 5) Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. The nomenclature assigned to the olfactory receptor genes and proteins for this organism is independent of other organisms. [provided by RefSeq, Jul 2008]

OR52N5 links:

TRIM5 (HGNC:16276): (tripartite motif containing 5) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The protein forms homo-oligomers via the coilel-coil region and localizes to cytoplasmic bodies. It appears to function as a E3 ubiquitin-ligase and ubiqutinates itself to regulate its subcellular localization. It may play a role in retroviral restriction. Multiple alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Dec 2009]

TRIM5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.41892573).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR52N5	NM_001385662.1 linkuse as main transcript	c.201G>A	p.Met67Ile	missense_variant	3/3	ENST00000641181.1
OR52N5	NM_001001922.2 linkuse as main transcript	c.201G>A	p.Met67Ile	missense_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR52N5	ENST00000641181.1 linkuse as main transcript	c.201G>A	p.Met67Ile	missense_variant	3/3		NM_001385662.1	P1
TRIM5	ENST00000412903.1 linkuse as main transcript	c.-61-98196G>A		intron_variant		1
OR52N5	ENST00000317093.2 linkuse as main transcript	c.201G>A	p.Met67Ile	missense_variant	1/1			P1
TRIM5	ENST00000380027.5 linkuse as main transcript	c.-441+77318G>A		intron_variant		5			Q9C035-4

Frequencies

GnomAD3 genomes

AF:

0.0000289

AC:

AN:

138262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000319

Gnomad OTH

AF:

0.00108

GnomAD3 exomes

AF:

0.00000424

AC:

AN:

236084

Hom.:

AF XY:

0.00000784

AC XY:

AN XY:

127570

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000938

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000799

AC:

AN:

1376412

Hom.:

Cov.:

AF XY:

0.0000102

AC XY:

AN XY:

684942

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000105

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000289

AC:

AN:

138262

Hom.:

Cov.:

AF XY:

0.0000446

AC XY:

AN XY:

67228

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000319

Gnomad4 OTH

AF:

0.00108

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2024

The c.201G>A (p.M67I) alteration is located in exon 1 (coding exon 1) of the OR52N5 gene. This alteration results from a G to A substitution at nucleotide position 201, causing the methionine (M) at amino acid position 67 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Benign

-0.076

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.015

T;T

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.20

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.89

.;D

M_CAP

Benign

0.0082

MetaRNN

Benign

0.42

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.7

H;H

MutationTaster

Benign

1.0

D;N

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-3.5

.;D

REVEL

Benign

0.21

Sift

Uncertain

0.0010

.;D

Sift4G

Pathogenic

0.0010

.;D

Polyphen

0.024

B;B

Vest4

0.49

MutPred

0.39

Loss of glycosylation at P66 (P = 0.2907);Loss of glycosylation at P66 (P = 0.2907);

MVP

0.24

MPC

0.081

ClinPred

0.85

GERP RS

2.6

Varity_R

0.86

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over